| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Post-surgical neuropathic pain (PSNP) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Post-surgical neuropathic pain (PSNP) |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10054095 |
| E.1.2 | Term | Neuropathic pain |
| E.1.2 | System Organ Class | 100000004852 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To demonstrate superiority of Qutenza over low-dose capsaicin control in change from baseline to Week 12 in the 24-hr average pain intensity in subjects with PSNP. |
|
| E.2.2 | Secondary objectives of the trial |
Core Phase:
• To demonstrate superiority of Qutenza over low-dose capsaicin control in change from baseline to Week 12 in treatment area size in subjects with PSNP.
• To assess the safety and tolerability of Qutenza in subjects with PSNP.
Extension Phase:
• To confirm the long-term efficacy of Qutenza in subjects with PSNP.
• To assess the long-term safety and tolerability of Qutenza in subjects with PSNP. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
General
1. The subject has given written informed consent to participate.
2. Female or male subjects aged 18 years or older.
3. For women of childbearing potential: negative pregnancy tests at Screening Visit (Visit 1), the Randomization Visit (Visit 2), and prior to each reapplication of the IMP, and must have agreed to practice medically acceptable methods of birth control.
Confirmation of diagnosis of chronic moderate to severe PSNP (see also Protocol Table 1)
4. Documented diagnosis of PSNP by the following criteria:
a. A history of post-surgical pain with a duration of at least 6 months to maximally 60 months that is plausibly related to the surgical intervention as documented on a body map.
b. DN4i of at least 3 out of 7 points at Visit 1.
c. The pain must extend beyond the scar area to neuroanatomically adjacent skin areas and be related to the site of the surgery.
5. Documented diagnosis of probable or definite PSNP according to the following criteria:
a. The pain must be associated with sensory signs in the same neuroanatomically plausible distribution. The area of sensory changes may extend beyond, be within, or overlap with the area of pain (criterion for probable neuropathic pain), or
b. In addition to 5a : Direct surgical evidence (e.g., surgeon´s clear verification of an intraoperative nerve lesion) (criterion for definite neuropathic pain).
6. The subject has moderate to severe pain with a baseline value for 24-hr average pain intensity of at least 4 points on the NPRS. The baseline value is calculated as the average of the 24-hr average pain intensity ratings of the Baseline Phase (Day -7 to Day -1). At least 5 (out of the last 7 days) pain ratings should be available during the Baseline Phase. If less than 5 pain ratings are available in the last 7 days, the subject may be rescheduled for Visit 2 (1 time only) after having received appropriate re-training in the use of the e-diary to ensure compliance.
Suitability for treatment with IMP
7. The size of the affected painful intact skin area is not larger than the size of 4 standard Qutenza topical systems (1120 cm2).
8. The skin in the area where the IMP will be applied, and that may also contain the scar tissue, is intact, dry, and non-irritated (i.e., there are no signs and symptoms of skin disease, skin irritation, inflammation or injury, such as active herpes zoster lesions, atopic dermatitis, ulceration, wounds). This is reflected by a dermal assessment score of 0 = "no evidence of irritation" or 1 = "minimal erythema, barely perceptible".
Eligibility with regard to protocol adherence, to allowed pre-treatments and concomitant treatments
9. The subject is willing to adhere to the restricted use of concomitant treatments (see concomitant treatments in Section 1.4.2).
10. The subject experiencing pain is:
a. currently not receiving treatment for PSNP or
b. receives a stable systemic treatment for PSNP that started more than 30 days prior to the Randomization Visit (Visit 2). |
|
| E.4 | Principal exclusion criteria |
General or previous treatments
1. The subject received Qutenza before the Randomization Visit (Visit 2) or received a medical device in another clinical trial within 7 days before the Randomization Visit (Visit 2), or
a. Any former use of topical capsaicin in the area of the PSNP before Visit 2, except for the use of a low-dose (<1%) capsaicin product – but not within 7 days before Visit 2.
b. The subject participated previously in this clinical trial or participated in another clinical trial for the treatment of PSNP completing less than 3 months ago.
2. A score of 0 out of 5 in all 3 categories of the neurological/sensory examinations, i.e., for warm sensation, pinprick and cold sensation at the Screening Visit (Visit 1).
Confounding factors
3. The subject reported a 24-hr average pain intensity score of 10 on the NPRS for at least 4 days during the Baseline Phase.
4. Any painful procedure planned during the course of the trial that may, in the opinion of the investigator, affect the efficacy or safety assessments.
5. Subjects with PSNP related to a surgery/condition with a high potential for confounding symptoms, e.g., the pain is at least partially due to pain in deeper structures such as muscles or bones (including referred pain from deeper structures) as listed in examples in
Protocol Table 2.
6. Other painful conditions in the body area that is affected by PSNP and may affect efficacy or safety assessments and cannot be discriminated from the target pain by subject, including infectious, non-infectious, inflammatory or neuropathic conditions which could also be complications related to the previous surgical procedure.
Contraindications to IMP
7. Neuropathic pain areas located only on the face, above the hairline of the scalp, and/or in proximity to mucous membranes.
8. Hypersensitivity to capsaicin (i.e., chili peppers or over-the-counter [OTC] capsaicin products), or to any excipients of the IMP or to excipients of the cleansing gel in use and their components, or to topical anesthetics in use and their components.
Medical history/concurrent condition(s)/other factors
9. Pending litigation due to chronic pain or disability.
10. The subject has a history of alcohol or drug abuse or is actively abusing drugs (including alcohol, medication) during the 1 year prior to the Screening Visit (Visit 1) as judged by the investigator.
11. Evidence or history of severe psychiatric illness/disorder during the 3 years prior to the Screening Visit (Visit 1) that, in the investigator’s opinion, may affect efficacy or safety assessments or may compromise the subject’s safety during trial participation, e.g., major depression, major anxiety disorder, psychosis, severe personality disorders.
12. Evidence of cognitive impairment including dementia that may interfere with the subject’s ability to complete pain assessments requiring recall of the average pain level in the past 24 hrs.
13. Surgical intervention in the last 3 months preceding the Screening Visit (Visit 1) if it is affecting the efficacy or safety assessments, or any scheduled or planned surgery during the trial, with the exception of the Extension Phase if the planned surgery is not expected to affect the efficacy or safety assessments.
14. Patients with current clinically significant disease(s) or condition(s) (including clinically significant cardiovascular disease and/or significant pain in other areas) that may affect efficacy or safety assessments, or any other reason which, in the investigator’s opinion, may preclude the subject’s participation in the full duration of the trial. Patients with current signs and symptoms consistent with Coronavirus disease 2019 (COVID-19) (e.g., dry cough, dyspnea, sore throat, fatigue, fever) or subjects who had those symptoms within the last 14 days prior to screening and had a positive SARS-CoV2 PCR test result.
15. Unstable or poorly controlled blood pressure which, in the opinion of the investigator, would put the subject at risk of severe adverse blood pressure increases upon IMP application.
16. Known or suspected of not being able to comply with the requirements of the trial protocol or the instructions of the trial site staff.
17. Not able to communicate meaningfully with the trial site staff.
18. The subject is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, or is a family member of the employees or the investigator. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline to the average score of the entire period between Week 2 and Week 12 in the 24-hr average pain intensity. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| from the Baseline Phase (Day -7 to Day -1) to Visit 6 (Week 12/Day 84). |
|
| E.5.2 | Secondary end point(s) |
Core Phase:
1. Change from baseline to Week 12 in the treatment area size.
2. Incidence of treatment-emergent adverse events (TEAEs). Incidence of TEAEs leading to discontinuation in the Core Phase.
Extension Phase:
1. Change from baseline to the weekly average score of Week 42 in the 24-hr average pain intensity.
2. Change from baseline to Week 42 in the treatment area size.
3. Change from baseline to the average score of the entire period between Week 2 and Week 42 in the 24-hr average pain intensity.
4. Incidence of TEAEs. Incidence of TEAEs leading to discontinuation in the Extension Phase. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Core Phase
1. At Visit 2 (Day 1) before IMP application and at Visit 6 before IMP application (Week 12/Day 84)
2. Documentation of TEAEs from the start of treatment at Visit 2(Day 1) up to the time of the last scheduled contact in the Core Phase of the Treatment Period
Extension Phase
1.From the Baseline Phase(Day -7 to Day -1) to Final Visit(Week 42/Day 294)
2.At Visit 2 (Day 1) before IMP application and at Visit 6 before IMP application (Week 12/Day 84)
3.From the Baseline Phase (Day -7 to Day -1) to the Final Visit(Week 42/Day 294)
4.Documentation of TEAEs from start of treatment at Visit 2(Day 1) up to the time of the last scheduled contact in the Extension Phase of the Treatment Period |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United States |
| France |
| Poland |
| United Kingdom |
| Netherlands |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The trial-related end of the trial is defined as the date of last subject out.
The subject-related end of trial is defined as date of last contact with the subject according to the protocol. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | 4 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 5 |
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